6-2765854-TCG-CTA

Variant names:

• chr6-2765854-TCG-CTA
• NM_020135.3:c.232_234delTCGinsCTA
• WRNIP1 p.Ser78Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_020135.3(WRNIP1):​c.232_234delTCGinsCTA​(p.Ser78Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WRNIP1 NM_020135.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11
• Publications: 0 publications found

Genes affected

WRNIP1 (HGNC:20876): (WRN helicase interacting protein 1) Werner's syndrome is a rare autosomal recessive disorder characterized by accelerated aging that is caused by defects in the Werner syndrome ATP-dependent helicase gene (WRN). The protein encoded by this gene interacts with the exonuclease-containing N-terminal portion of the Werner protein. This protein has a ubiquitin-binding zinc-finger domain in the N-terminus, an ATPase domain, and two leucine zipper motifs in the C-terminus. It has sequence similarity to replication factor C family proteins and is conserved from E. coli to human. This protein likely accumulates at sites of DNA damage by interacting with polyubiquinated proteins and also binds to DNA polymerase delta and increases the initiation frequency of DNA polymerase delta-mediated DNA synthesis. This protein also interacts with nucleoporins at nuclear pore complexes. Two transcript variants encoding different isoforms have been isolated for this gene. [provided by RefSeq, Jul 2012]

MYLK4 (HGNC:27972): (myosin light chain kinase family member 4) Predicted to enable myosin light chain kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020135.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WRNIP1	NM_020135.3	MANE Select	c.232_234delTCGinsCTA	p.Ser78Leu	missense	N/A	NP_064520.2
	WRNIP1	NM_130395.3		c.232_234delTCGinsCTA	p.Ser78Leu	missense	N/A	NP_569079.1	Q96S55-2
	MYLK4	NM_001347872.2		c.56+4202_56+4204delCGAinsTAG		intron	N/A	NP_001334801.1	A0A8V8TMV3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WRNIP1	ENST00000380773.9	TSL:1 MANE Select	c.232_234delTCGinsCTA	p.Ser78Leu	missense	N/A	ENSP00000370150.4	Q96S55-1
	WRNIP1	ENST00000618555.4	TSL:1	c.232_234delTCGinsCTA	p.Ser78Leu	missense	N/A	ENSP00000477551.1	Q96S55-1
	WRNIP1	ENST00000380771.8	TSL:1	c.232_234delTCGinsCTA	p.Ser78Leu	missense	N/A	ENSP00000370148.4	Q96S55-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-2766088;